HHMI News

[ May 15, 2013 ]

Malaria Parasites Communicate to Coordinate Behavior

Summary

Malaria parasites infecting human red blood cells send packets of information between cells to coordinate group activity. When the parasites are under stress, the communication increases their ability to develop into a new stage of the life cycle.

Highlights

Malaria parasites inside a human host must differentiate into a new, sexual form to be transmitted back to a mosquito.

When infected human cells were exposed to an anti-malarial drug in laboratory experiments, placing the parasites under stress, more communication vesicles were produced. The communication increases the parasites’ ability to develop into a new stage of the life cycle.

Malaria parasites infecting human red blood cells send packets of information between cells to coordinate group activity, HHMI senior international research scholar Alan Cowman has discovered. When the parasites are under stress—such as when they’re exposed to antimalarial drugs—the communication increases the parasites’ ability to develop into a new stage of their life cycle.

Blocking the chatter could be a novel way to combat malaria infections and stop the spread of the disease, says Cowman, whose lab is at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. The new research was published online May 15, 2013, in the journal Cell.

The takeaway here is that these parasites are complex. They have a mechanism to really sense their environment in humans and let each other know what’s going on and what the right time to
develop is.

Alan F. Cowman

Malaria parasites, protozoa in the genus Plasmodium, have a complex life cycle that’s split between time in a human host and time in a mosquito. The disease, which affects more than 200 million people around the world, is spread when an infected mosquito bites a person. Inside a human, the parasite matures, reproduces, begins to cause symptoms, and eventually must differentiate into a new, sexual form to be transmitted back to a mosquito.

The finding that malaria parasites communicate inside their human hosts is so unexpected that when postdoctoral researcher Neta Regev-Rudzki first approached Cowman with a proposal to study how malaria parasites communicate with each other, Cowman admits he was skeptical that she’d find anything.

“I said, that’s impossible, it doesn’t happen,” he recalls. “But I figured I’d let her work on it for two or three months, she’d find out that it didn’t work, and we’d come up with a new project.”

But after a few months, just the opposite happened: it became surprisingly clear that communication was, in fact, happening between parasites. Regev-Rudzki had set up experiments using malaria parasites with different genetic or fluorescent markers and observed that the markers were repeatedly passed between parasites.

So Cowman’s lab started probing how this genetic information could be passed. By separating parasite-infected cells into containers with physical barriers, they quickly discovered that the cells didn’t need to touch one another for the parasites to transmit the markers. And when the researchers used a powerful atomic force microscope to zoom in on the liquid between parasites, they spotted small, membrane-surrounded packets, or vesicles. When they isolated these vesicles and mixed them with fresh malaria parasites, the genetic information was once again transferred.

“That really proved to me that this was happening,” says Cowman. “Parasites were transmitting information through these vesicles.”

Next, the scientists made another chance observation: shortly after each experiment in which vesicles were produced, all the parasites matured into their sexual form, the stage of the lifecycle in which they can be transmitted back to a mosquito. “That didn’t really make sense at first,” says Cowman. “These parasites were drug-resistant and should have been able to continue thriving in their old form.”

But another set of experiments revealed that the largest number of communication vesicles were produced when infected cells were exposed to an antimalarial drug, putting the parasites under stress. “It began to make sense then,” Cowman explains, “because if the parasites begin to be under stress, it’s advantageous for them to move to a different host.”

The team hasn’t yet characterized the contents of the information packets that zip between parasites, but they pinpointed one gene that’s required for the malaria parasites to produce the vesicles. When they blocked this gene, few parasites matured into the sexual form, an outcome that suggests that the pathway could contain ideal drug targets.

“A big aim among malaria researchers is to not only develop ways to treat the disease, but to make compounds that inhibit transmission,” says Cowman. “Blocking the passage of the parasites into the form that can spread to mosquitoes is one way to do that.”

Cowman’s lab is now not only working toward identifying what’s inside the vesicles, but finding more proteins and genes required for the communication that could be potential drug targets.

“The takeaway here is that these parasites are complex,” says Cowman. “They have a mechanism to really sense their environment in humans and let each other know what’s going on and what the right time to develop is.”